PPARα/γ-Independent Effects of PPARα/γ Ligands on Cysteinyl Leukotriene Production in Mast Cells

Peroxisome proliferator-activated receptor (PPAR) alpha ligands (Wy-14,643, and fenofibrate) and PPAR gamma ligands (troglitazone and ciglitazone) inhibit antigen-induced cysteinyl leukotriene production in immunoglobulin E-treated mast cells. The inhibitory effect of these ligands on cysteinyl leukotriene production is quite strong and is almost equivalent to that of the anti-asthma compound zileuton. To develop new aspects for anti-asthma drugs the pharmacological target of these compounds should be clarified. Experiments with bone-marrow-derived mast cells from PPAR alpha knockout mice and pharmacological inhibitors of PPAR gamma suggest that the inhibitory effects of these ligands are independent of PPARs alpha and gamma. The mechanisms of the PPAR-independent inhibition by these agents on cysteinyl leukotriene production are discussed in this review. Copyright (C) 2008 Masamichi Yamashita.